Selective activation and inhibition of calmodulin-dependent enzymes by a calmodulin-like protein found in human epithelial cells.
A calmodulin-like protein, which is identical in size and 85% identical to vertebrate calmodulin, was recently identified by 'subtractive hybridization' comparison of transcripts expressed in normal versus transformed human mammary epithelial cells. Unlike the ubiquitous distribution of calmodulin, calmodulin-like protein expression is restricted to certain epithelial cells, and appears to be modulated during differentiation. In addition, calmodulin-like protein levels are often significantly reduced in malignant tumor cells as compared to corresponding normal epithelial cells. The current studies compare calmodulin-like protein functions with those of calmodulin. We find that calmodulin-like protein activation of multifunctional Ca2+/calmodulin-dependent protein kinase II (calmodulin kinase II) is equivalent to activation by calmodulin, but that four other calmodulin-dependent enzymes, cGMP phosphodiesterase, calcineurin, nitric-oxide synthase, and myosin-light-chain kinase, display much weaker activation by calmodulin-like protein than by calmodulin. In the case of myosin-light-chain kinase, calmodulin-like protein competitively inhibits calmodulin activation of the enzyme with a Ki value of 170 nM. Thus, calmodulin-like protein may have evolved to function as a specific agonist of certain calmodulin-dependent enzymes, and/or as a specific competitive antagonist of other calmodulin-dependent enzymes.
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- Phosphoprotein Phosphatases
- Nitric Oxide Synthase
- Myosin-Light-Chain Kinase
- Molecular Sequence Data
- Humans
- Female
- Epithelium
- Enzyme Inhibitors
- Enzyme Activation
- Chromatography, Affinity
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Phosphoprotein Phosphatases
- Nitric Oxide Synthase
- Myosin-Light-Chain Kinase
- Molecular Sequence Data
- Humans
- Female
- Epithelium
- Enzyme Inhibitors
- Enzyme Activation
- Chromatography, Affinity